Psychotic disorders are a group of serious mental illnesses with an average age of onset in late adolescence or early adulthood. The most common psychotic, disorders include schizophrenia, bipolar disorder with psychotic features, major depression with psychotic features. Psychotic disorders are primarily characterized by the presence of hallucinations, delusions (such as hearing voices and paranoia) and related changes in behaviour.
Schizophrenia represents the majority of psychotic disorders (about 80%). In 1990, Schizophrenia was estimated to be the 10th leading cause of non-fatal burden in the world, accounting for 2.6% of total “years of life lived with disability” (YLD), around the same percentage as congenital malformations. The Global Burden of Disease 2000 study found the disease to be the 7th leading cause of YLDs at the global level, accounting for 2.8% of total global YLD.
Whilst the potential benefit of preventing psychotic disorders is great, currently available strategies for prevention by treating attenuated symptoms with pharmacological psychiatric interventions (e.g., antipsychotics, antidepressants, mood stabilizers) are not ideal.
Previous trials have investigated the preventive use of antipsychotic medications in ultra-high-risk groups. One study for example showed that a combination of risperidone and cognitive therapy for 8 months was significantly more effective than supportive counselling at end of intervention, but not at 12-month follow-up. A second study, compared 12 months intervention with olanzapine to placebo and found no significant intervention group differences. It was concluded that the benefits of pre-onset intervention with antipsychotics may outweigh the risks to a degree sufficient to endorse future trials. However, the use or antipsychotic medication for indicated prevention remains controversial even in research settings because of the high number of false positives (about 70-80% of people who meet ultra-high-risk criteria do not progress to psychotic disorder within one year). Somatization associated with the use antipsychotics, and unwanted side effects which include metabolic changes, sexual dysfunction and weight gain are often not acceptable. Other side effects may include dyslipidaemia, cardiac arrhythmia and osteoporosis.
The use of such medication as a preventative therapy is controversial because there is no certainty that patients at risk of developing the psychosis will go or) to develop the disease. Many patients fail to respond to these medications or only to a limited degree. None of these available medicines reliably produce a complete remission of symptoms.
The diagnostic criteria used to identify individuals at risk for psychotic disorders is imprecise, particularly given that not all individuals assessed at high risk will transition to a psychotic disorder within one year. The transition rate for individuals may vary between 5%-40% depending on the population which the risk is assessed against. Therefore pharmacological interventions are not ideal since not all individuals may benefit in the long term and would also lead to unnecessary costs and waste of resources.
In order to lower the risk of individuals transitioning to psychosis or a psychotic disorder, intervention therapies are needed. There is also a need for intervention therapies that reduce or minimise biological or psychosocial damage that manifests during the onset of psychotic disorders. There is also a need for preventative therapies with minimal risk of unwanted side-effects and also with a sustained therapeutic effect.
In contrast, omega-3 polyunsaturated fatty acids (PUPA) have been shown to be very safe even when used in relatively high doses and except from gastrointestinal symptoms like fishy eructation, nausea and loose stools which may occur, they are free of clinically relevant side effects. They have the advantage of excellent tolerability, public acceptance, relatively low costs, and benefits for general health.
Some therapeutic effects of omega-3 PUFA on cardiovascular diseases are already well known. It has also been suggested that these PUFAs are essential for normal pre-natal of post-natal development of retina and the brain.
U.S. Pat. No. 6,384,077 (Peet et al) describes a method of treating schizophrenia and related disorders in patients diagnosed as already having the disorder by administration of highly purified eicosapentanoic acid (EPA) in combination with a drug that acts primarily on neurotransmitter metabolism of receptors. The composition used in this method contains at least 90% or more EPA, and less than 5% docosahexaenoic acid (DHA).
US 2007/0161705 (Bruzzese) describes use of omega-3 PUFA, including a mixture of DHA and EPA for prevention and/or treatment, of disturbances of the central nervous system including schizophrenia.
Although it is known to a certain degree that compositions comprising combinations of omega-3 PUFA may have shown effectiveness in the treatment of mental disorders, none of the literature provide a reasonable expectation that the use of such omega-3 fatty acids may prevent or delay the onset of such diseases in individuals assessed at ultra high risk of developing a psychotic disorder. Moreover, there is no published evidence that such treatment could have long term benefits for certain individuals, after the treatment or intervention has ceased.
The present invention seeks to at least minimise one of the above limitations and/or address these needs.